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      Cochlea sparing effects of intensity modulated radiation therapy in head and neck cancers patients: a long-term follow-up study

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          Abstract

          Background

          Radiation to the inner ear may lead to (irreversible) sensorineural hearing loss. The purpose of this study was to evaluate the long-term effect of radiotherapy on hearing in patients treated with Intensity Modulated Radiation Therapy (IMRT), sparing the inner ear from high radiation dose as much as possible.

          Methods

          Between 2003 and 2006, 101 patients with head and neck cancer were treated with IMRT. Audiometry was performed before, short-term, and long-term after treatment. Data were compared to normal hearing levels according to the International Organisation for Standardization (ISO). Statistical analysis was done using repeated measurements. None of the patients received chemotherapy.

          Results

          In 36 patients an audiogram at long-term follow-up (median 7.6 years) was available. The mean dose to the cochlea was 17.8 Gy (1.0-66.6 Gy). A hearing deterioration of 1.8 dB at Pure Tone Average (PTA) 0.5-1-2 kHz ( p = 0.11), 2.3 dB at PTA 1-2-4 kHz ( p = 0.02), and 4.4 dB at PTA 8-10-12.5 kHz ( p = 0.01) was found. According to the ISO, the expected age-related hearing loss was 2.7, 4.8, and 8.8 dB at PTA 0.5-1-2 kHz, 1-2-4 kHz, and 8-10-12.5 kHz, respectively.

          Conclusions

          After IMRT with radiation dose constraint to the cochlea, potential long-term adverse effects of IMRT remained subclinical. The progressive hearing loss over time was mild and could be attributed to the natural effects of ageing. Therefore, we recommend that a dose constraint to the cochlea should be incorporated in the head and neck radiotherapy protocols.

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          Most cited references19

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          A prospective, randomized study comparing outcomes and toxicities of intensity-modulated radiotherapy vs. conventional two-dimensional radiotherapy for the treatment of nasopharyngeal carcinoma.

          To compare clinical outcomes and toxicities of two-dimensional conventional radiation therapy (2D-CRT) and intensity modulated radiation therapy (IMRT) for the treatment of nasopharyngeal carcinoma (NPC). Between July 2003 and October 2008, 616 patients with non-metastatic stage I to IVb NPC were prospectively randomized to receive 2D-CRT (n=310; mean age, 44.8±13.6 years) or IMRT (n=306; mean age, 46.7±12.5 years). Clinical outcomes and acute and late toxicities were determined and compared. The 2 groups were comparable with respect to all parameters of demographics and disease characteristics (all, p>0.05). Median follow-up was 42 months (range, 1-83 months). The 5-year actuarial local control rate was 90.5% in the IMRT group and 84.7% in the 2D-CRT group. The local control rates were 91% for stage T3 and 81.5% for stage T4 disease in the IMRT group and 80% and 62.2% in the 2D-CRT group, respectively. The 5-year actuarial nodal relapse-free survival (NRFS) rate was 92.4% in the IMRT and 92.9% in the 2D-CRT group (p>0.05). The NRFS was 93.9% for N2 disease in the IMRT group and 91.4% in the 2D-CRT group (p=0.02). The 5-year overall survival (OS) rate was 79.6% for the IMRT group and 67.1% for the 2D-CRT group (p=0.001). When stratified for stage, a significant difference was only noted for stage III disease. In terms of radiation-induced toxicities, patients in IMRT group had significantly lower radiation-induced toxicities than those in 2D-CRT group. IMRT provides improved local-recurrence free survival, especially in late-stage NPC patients and is associated with a lower incidence of toxicities. Copyright © 2012. Published by Elsevier Ireland Ltd.
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            Xerostomia and quality of life after intensity-modulated radiotherapy vs. conventional radiotherapy for early-stage nasopharyngeal carcinoma: initial report on a randomized controlled clinical trial.

            To compare directly the effect of intensity-modulated radiotherapy (IMRT) vs. conventional radiotherapy (CRT) on salivary flow and quality of life (QoL) in patients with early-stage nasopharyngeal carcinoma (NPC). Fifty-one patients with T2, N0/N1, M0 NPC took part in a randomized controlled clinical study and received IMRT or CRT. Stimulated whole (SWS) and parotid (SPS) saliva flow were measured and Medical Outcomes Short Form 36 (SF-36), European Organization for Research and Treatment of Cancer (EORTC) core quetionnaire, and EORTC head-and-neck module (QLQ-H&N35) were completed at baseline and 2, 6, and 12 months after radiotherapy. Forty-six patients (88%) were in disease remission 12 months after radiotherapy. At 12 months postradiotherapy, 12 (50.0%) and 20 patients (83.3%) in the IMRT group had recovered at least 25% of preradiotherapy SWS and SPS flow respectively, compared with 1 (4.8%) and 2 patients (9.5%), respectively, in the CRT group. Global health scores showed continuous improvement in QoL after both treatments (p < 0.001). However, after 12 months subscale scores for role-physical, bodily pain, and physical function were significantly higher in the IMRT group, indicating a better condition (p < 0.05). Dry mouth and sticky saliva were problems in both groups 2 months after treatment. In the IMRT group, there was consistent improvement over time with xerostomia-related symptoms significantly less common than in the CRT group at 12 months postradiotherapy. IMRT was significantly better than CRT in terms of parotid sparing and improved QoL for early-stage disease. The findings support the case for assessment of health-related QoL in relation to head-and-neck cancer using a site-specific approach.
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              Radiation therapy and hearing loss.

              A review of literature on the development of sensorineural hearing loss after high-dose radiation therapy for head-and-neck tumors and stereotactic radiosurgery or fractionated stereotactic radiotherapy for the treatment of vestibular schwannoma is presented. Because of the small volume of the cochlea a dose-volume analysis is not feasible. Instead, the current literature on the effect of the mean dose received by the cochlea and other treatment- and patient-related factors on outcome are evaluated. Based on the data, a specific threshold dose to cochlea for sensorineural hearing loss cannot be determined; therefore, dose-prescription limits are suggested. A standard for evaluating radiation therapy-associated ototoxicity as well as a detailed approach for scoring toxicity is presented. Copyright 2010 Elsevier Inc. All rights reserved.
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                Author and article information

                Contributors
                Journal
                J Otolaryngol Head Neck Surg
                J Otolaryngol Head Neck Surg
                Journal of Otolaryngology - Head & Neck Surgery
                BioMed Central
                1916-0208
                1916-0216
                2014
                6 August 2014
                : 43
                : 1
                : 30
                Affiliations
                [1 ]Department of Head and Neck Oncology and Surgery, The Netherlands Cancer Institute, Plesmanlaan 121, Amsterdam, 1066, CX, The Netherlands
                [2 ]Department of Maxillofacial Surgery, Academic Medical Center, University of Amsterdam, Meibergdreef 9, Amsterdam, 1105, AZ, The Netherlands
                [3 ]Department of Epidemiology and Biostatistics, The Netherlands Cancer Institute, Plesmanlaan 121, Amsterdam, 1066, CX, The Netherlands
                [4 ]Department of Otorhinolaryngology, Academic Medical Center, University of Amsterdam, Meibergdreef 9, Amsterdam, 1105, AZ, The Netherlands
                [5 ]Department of Medical Oncology, The Netherlands Cancer Institute, Plesmanlaan 121, Amsterdam, 1066, CX, The Netherlands
                [6 ]Department of Radiation Oncology, Academic Medical Center, University of Amsterdam, Meibergdreef 9, Amsterdam, 1105, AZ, The Netherlands
                [7 ]Department of Audiology, Academic Medical Center, University of Amsterdam, Meibergdreef 9, Amsterdam, 1105, AZ, The Netherlands
                Article
                s40463-014-0030-x
                10.1186/s40463-014-0030-x
                4746991
                25095702
                8bcae7b6-b96d-4dec-bdd2-0cdfdda88eed
                Copyright © 2014 Theunissen et al.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 2 April 2014
                : 14 July 2014
                Categories
                Original Research Article

                radiotherapy,imrt,hearing loss,cochlea
                radiotherapy, imrt, hearing loss, cochlea

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